The goals of the proposed resarch are to: (i) prepare monoclonal antibody that recognized tumor-associated or embryonal antigens on the surface of rat glioma cells; and, (ii) determine the safety and efficacy of using such antibody for diagnosis and/or treatment of primary brain tumors in a rat model system. Starting with rats that have been hyperimmunized to primary rat gliomas, we will hybridize, in vitro, their immune splenic B lymphocytes with cells from a mouse myeloma cell line to produce hybrid cell lines that elaborate monoclonal antibodies directed against glioma-associated antigens. From this panel of rat monoclonal antibodies we will select those that detect cell surface antigens unique to malignant glial cells. These antibodies will be characterized as to: (i) specificity against a wide variety of normal and malignant tissues, (ii) class and IgG subclass, and (iii) capacity to exert a tumor-specific cytotoxic effect on rat glioma cells in concert with complement or lymphoid cells. Using either externally (125I; 131I) or internally (3H-amino acid; 75Se-methionine) radiolabled antibody, we will determine the extent, and persistence, of in vivo localization of each antibody in rats bearing primary, autochlhonous, avian sarcoma virus-induced gliomas. If the degree of intratumoral localization is low or does not persist, we will achieve and sustain high levels by: (i) using de-aggregated antibody preparations, (ii) reversibly increasing the blood-brain barrier permeability, or, (iii) diminishing the potential problem of immune-complex formation. When we have developed the capacity to sustain high intratumoral levels of monoclonal anti-glioma antibodies, we will investigate the safety and efficacy of using these antibodies singly or in combinations with conventional therapies (radiation and chemotherapy) that have demonstrated value in significantly prolonging the survival of tumor-bearing rats. The results of these studies, if successful in significantly prolonging survival of tumor-bearing rats, will form the basis for a rational approach for immunotherapeutic intervention in the neoplastic process of man.